Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation.
Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation.
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DOI：
10.1002/glia.20793
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发表时间：
2009-04-15
期刊：
影响因子：
6.2
通讯作者：
Fiskum, Gary
中科院分区：
文献类型：
--
作者：
Danilov, Camelia A.;Chandirasekaran, Krish;Racz, Jennifer;Soane, Lucian;Zielke, Carol;Fiskum, Gary
氧化应激是脑缺血再灌注后星形胶质细胞损伤和死亡的重要分子机制，可能是一个有效的干预靶点。用于解毒在这些条件下产生的许多不同活性氧和氮物质的一种治疗策略是通过使用促进转录激活因子NRF 2从细胞质移位到细胞核的化学品或条件来诱导II期基因应答，在细胞核中转录激活因子NRF 2与基因组抗氧化应答元件结合。本研究测试了一种假设，即用萝卜硫素（一种已知可激活NRF 2基因表达途径的烷化剂）对培养的皮质星形胶质细胞进行预处理或后处理，可防止因短暂暴露于O2和葡萄糖剥夺（OGD）引起的星形胶质细胞死亡。大鼠皮质星形胶质细胞在OGD前48小时或OGD后48小时暴露于5 μM莱菔硫烷。预处理和后处理均显著减少OGD后48小时的细胞死亡。8-羟基-2-脱氧鸟苷的免疫染色，DNA/RNA氧化的标志物，减少在4小时复氧与莱菔硫烷预处理。萝卜硫素暴露后，细胞和核NRF 2免疫反应性增加。此外，萝卜硫素还增加了NADPH/醌氧化还原酶1（NRF 2转录激活的已知靶点）的mRNA、蛋白质水平和酶活性。我们的结论是，萝卜硫素刺激NRF 2途径的抗氧化基因表达的星形胶质细胞，并保护他们从细胞死亡在体外模型缺血/再灌注。
Oxidative stress is an important molecular mechanism of astrocyte injury and death following ischemia reperfusion and may be an effective target of intervention. One therapeutic strategy for detoxifying the many different reactive oxygen and nitrogen species that are produced under these conditions is induction of the Phase II gene response by the use of chemicals or conditions that promote the translocation of the transcriptional activating factor NRF2 from the cytosol to the nucleus, where it binds to genomic antioxidant response elements. This study tested the hypothesis that pre- or post-treatment of cultured cortical astrocytes with sulforaphane, an alkylating agent known to activate the NRF2 pathway of gene expression protects against death of astrocytes caused by transient exposure to O2 and glucose deprivation (OGD). Rat cortical astrocytes were exposed to 5 μM sulforaphane either 48 hr prior to, or for 48 hr after a 4 hr period of OGD. Both pre- and post-treatments significantly reduced cell death at 48 hr after OGD. Immunostaining for 8-hydroxy-2-deoxyguanosine, a marker of DNA/RNA oxidation, was reduced at 4 hr reoxygenation with sulforaphane pretreatment. Sulforaphane exposure was followed by an increase in cellular and nuclear NRF2 immunoreactivity. Moreover, sulforaphane also increased the mRNA, protein level, and enzyme activity of NADPH/Quinone Oxidoreductase 1, a known target of NRF2 transcriptional activation. We conclude that sulforaphane stimulates the NRF2 pathway of antioxidant gene expression in astrocytes and protects them from cell death in an in vitro model of ischemia/reperfusion.
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影响因子：
14.9
作者：
Motohashi, H;Shavit, JA;Engel, JD
通讯作者：
Engel, JD
影响因子：
4.1
作者：
Ikeda, H;Serria, MS;Sakai, M
通讯作者：
Sakai, M
DOI：
10.1073/pnas.77.9.5216
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BENSON, AM;HUNKELER, MJ;TALALAY, P
通讯作者：
TALALAY, P
影响因子：
1.7
作者：
JUURLINK, BHJ;HERTZ, L;YAGER, JY
通讯作者：
YAGER, JY
DOI：
10.1097/00005072-199803000-00004
发表时间：
1998-03-01
影响因子：
3.2
作者：
Petito, CK;Olarte, JP;Pulsinelli, WA
通讯作者：
Pulsinelli, WA